Study of FF-10501-01 in Patients With Relapsed or Refractory Hematological Malignancies

NCT02193958 | Completed Phase 1 Results

• 1 other identifier: FF1050101US01
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase 1/2a Dose Escalation Study of FF-10501-01 in Patients with Relapsed or Refractory Hematological Malignancies to determine the safety and tolerability. A total of 6 cohorts will be enrolled in Phase 1 to establish the MTD. A total of 20 subjects with MDS/CMML treated at the RP2D are planned, including MDS/CMML subjects treated at the RP2D in Phase 1.

Conditions

AML; CMML; MDS

Keywords

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Safety Assessed by Adverse Events

  Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicity (DLT), dose reductions, delays or withdrawals due to toxicity

  12 months

Secondary Outcomes (1)

• Determination of Objective Response (OR) Rates.

  OR responses were assessed at end of Cycles 1 thru 3. Each cycle was 28 days in length.

Study Arms (9)

Phase 1 Cohort 1: 50mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Drug: FF-10501-01

Phase 1 Cohort 2: 100mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Drug: FF-10501-01

Phase 1 Cohort 3: 200mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Drug: FF-10501-01

Phase 1 Cohort 4: 300mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Drug: FF-10501-01

Phase 1 Cohort 5: 400mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Drug: FF-10501-01

Phase 1 Cohort 6: 500mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Drug: FF-10501-01

Phase 2a Cohort 7: 400mg/m2 in MDS/CMML

EXPERIMENTAL

FF-10501-01 tablets BID every 21 days of a 28-day cycle.

Drug: FF-10501-01

Phase 1 Cohort 8: 400mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 28 days of a 28 day cycle.

Drug: FF-10501-01

Phase 2a Cohort 9: 400mg/m2

EXPERIMENTAL

FF-10501-01 tablets BID every 21 days of a 28-day cycle.

Drug: FF-10501-01

Interventions

FF-10501-01 DRUG

FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.

Also known as: Single Group Assignment, Drug FF-10501-01

Phase 1 Cohort 1: 50mg/m2; Phase 1 Cohort 2: 100mg/m2; Phase 1 Cohort 3: 200mg/m2; Phase 1 Cohort 4: 300mg/m2; Phase 1 Cohort 5: 400mg/m2; Phase 1 Cohort 6: 500mg/m2; Phase 1 Cohort 8: 400mg/m2; Phase 2a Cohort 7: 400mg/m2 in MDS/CMML; Phase 2a Cohort 9: 400mg/m2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed advanced hematologic malignancies;
• Phase 1:
• High-risk MDS/CMML (defined as ≥ 10% peripheral blood or marrow blasts and/or IPSS score ≥ 1.5) and relapsed or refractory to prior therapy
• AML relapsed or refractory to prior therapy, or ≥ 60 years of age and not a candidate for other therapies
• Phase 2a:
• MDS/CMML, relapsed from, or refractory to, prior HMA therapy; the latter defined as failure to achieve clinical remission (CR), partial remission (PR) or hematologic improvement (HI) after previous HMA therapy (≥ 4 cycles of azacitidine or decitabine), or progression during, or toxicity to previous HMA therapy precluding further HMA treatment, and,
• Bone marrow blast count ≥ 10% or peripheral blast count ≥ 5%, or IPSS-R score ≥ 3.5.
• At least 3 weeks beyond the last chemotherapy, targeted anticancer agent, major surgery or experimental treatment and recovered from all acute toxicities (≤ Grade 1). Hydroxyurea used to control peripheral blast counts is permitted up to Day 7 of treatment on study.
• Adequate performance status: ECOG ≤ 2;
• Adequate renal and hepatic function:
• creatinine ≤ 2.0 mg/dL, or calculated creatinine clearance ≥ 45 mL/min
• total bilirubin ≤ 2 times the upper limit of normal (ULN)
• ALT/AST ≤ 2 times ULN
• Negative serum pregnancy test
• Ability to provide written informed consent

You may not qualify if:

• Known history of coronary artery disease, angina, myocardial infarction, congestive heart failure, cardiac arrhythmia or any other type of heart disease present within the last 6 months
• Known family history of hereditary heart disease
• QT interval corrected for rate (QTc) \> 450 msec on the electrocardiogram (ECG) obtained at Screening
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of anti-microbials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for the care of the patient.
• Presence of active central nervous system (CNS) leukemia. Subjects adequately treated for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for leukemia cells are eligible. Subjects with no history of CNS leukemia will not be required to undergo cerebrospinal fluid sampling for eligibility.
• Known positive for HIV, hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV).
• Active infection requiring IV anti-infective usage within the last 7 days prior to study treatment.
• Any other medical intervention or condition which could compromise adherence to study requirements or confound the interpretation of study results.
• Pregnant or breast-feeding.
• Treatment with any investigational product within 28 days prior to Screening.

Sponsors & Collaborators

• Fujifilm Pharmaceuticals U.S.A., Inc.: lead

Study Sites (2)

Cleveland Clinic at Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Garcia-Manero G, Pemmaraju N, Alvarado Y, Naqvi K, Ravandi F, Jabbour E, De Lumpa R, Kantarjian H, Advani A, Mukherjee S, Gerds A, Carraway HE, Nazha A, Iwamura H, Murase M, Bavisotto L, Kurman M, Maier G, Johansen M, Sekeres MA. Results of a Phase 1/2a dose-escalation study of FF-10501-01, an IMPDH inhibitor, in patients with acute myeloid leukemia or myelodysplastic syndromes. Leuk Lymphoma. 2020 Aug;61(8):1943-1953. doi: 10.1080/10428194.2020.1747065. Epub 2020 Apr 7.

  PMID: 32264726 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Vice President of Clinical Operations
• Organization: FUJIFILM Pharmaceuticals U.S.A, Inc.

fphucontact@fujifilm.com

(617) 945-3763

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2014
• First Posted: July 18, 2014
• Study Start: July 1, 2014
• Primary Completion: August 9, 2019
• Study Completion: October 15, 2019
• Last Updated: March 19, 2025
• Results First Posted: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)